VYNE Therapeutics Initiates Phase 2b Trial of BET Inhibitor VYN201 for Vitiligo

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VYNE Therapeutics Inc. announced the dosing of the first subject in its phase 2b clinical trial for VYN201, a novel BET (bromodomain and extra-terminal domain) inhibitor aimed at treating nonsegmental vitiligo. The trial will assess the safety and efficacy of VYN201, a topical gel administered once daily, in subjects with either active or stable nonsegmental vitiligo. VYN201 targets local treatment, aiming to provide significant benefits with low systemic exposure. The trial's design includes a 24-week double-blind, vehicle-controlled period, followed by a 28-week extension phase.¹

"This disease state has had marked, marked unmet need for many, many years. It has been overlooked by industry with respect to new therapies, and even the therapies that are coming through now are all based on one pharmacology," Iain Stuart, PhD, the chief scientific officer at VYNE said in a recent interview with Dermatology Times. "We think that's unacceptable. We think the potential for BET inhibition could be very broad, and not just in vitiligo, but into all the dermatologic and immunologic diseases. The very fact that we have shown the very first clinical dataset in an autoimmune disease, and it happened to be vitiligo, was particularly encouraging."²

Approximately 160 participants will be enrolled in the study, divided into 4 groups with a 1:1:1:1 ratio. Three groups will receive different concentrations of VYN201 (1%, 2%, and 3%), while the fourth group will receive a vehicle placebo. After the initial24 weeks, participants in the vehicle group will be re-randomized to one of the active treatment groups for the remaining 28 weeks.

Efficacy and Safety Measures

The primary efficacy endpoint is the proportion of subjects achieving at least a 50% improvement in the Facial Vitiligo Area Scoring Index (F-VASI50) at week 24 compared to the vehicle group. Secondary endpoints include additional assessments of F-VASI and Total VASI (T-VASI) at both 24 and 52 weeks.

Previous Findings and Expectations

David Domzalski, president and chief executive officer of VYNE, highlighted the significance of this milestone, citing promising results from the prior phase 1b trial where VYN201 showed rapid onset of action and favorable safety with low systemic exposure. "We believe that VYN201 has the potential to become a valuable and differentiated therapy for patients with vitiligo," Domzalski stated in a press release. The company anticipates releasing top-line data from the initial 24-week treatment period by mid-2025.

VYN201

VYN201 is a locally administered pan-bromodomain BET inhibitor, designed as a “soft” drug to target diseases driven by multiple inflammatory pathways while minimizing systemic exposure. Preclinical studies have shown that VYN201 can reduce pro-inflammatory biomarkers and improve disease severity, demonstrating its potential across various inflammatory conditions.

BET Inhibitors

BET proteins are crucial in regulating gene transcription through epigenetic interactions. They play a significant role in B and T cell activation and subsequent inflammatory responses. BET inhibitors can block the transcription of pro-inflammatory cytokines, offering therapeutic potential in treating a range of immuno-inflammatory and fibrotic diseases, as well as certain myeloproliferative neoplastic disorders.

Phase 1b Insights from the Scientific Director

Stuart and his team recently presented pre-clinical and phase 1b data demonstrating promise in nonsegmental vitiligo at the Society for Investigative Dermatology Annual Meeting in Dallas, Texas.

He said, “We summarized the key data from an open-label phase 1b study with VYN201 where we were treating patients with nonsegmental vitiligo. That was for once-daily treatment for 16 weeks. It was an open-label trial. Obviously being a phase 1 study, the primary objective was safety, tolerability, and pharmacokinetics. We treated up to 29 patients across 3 cohorts, and we treated topically applied medications 0.5%, 1%, and 2%, so we actually saw some substantial improvement on vitiligo on the face. We really used that as our primary endpoint. We also saw great improvement there at our 1% and our 2% cohorts, and a very rapid onset of action, which was particularly encouraging, particularly when vitiligo studies take so long to see real recovery and pigmentation. That's one of the challenges of managing patients with vitiligo.

At the 16-week timepoint, we saw 39% improvement in our top dose of 2%. We also saw some very healthy movement and some key biomarkers from the non-facial areas. We took biopsies from lesions elsewhere on the body. Again, that helps support the hypothesis that VYN201 could potentially support the recovery of the pathway. We also saw a nice reduction of MMP-9, which is what we saw in our pre-clinical study. Again, that does support both an anti-inflammatory mechanism but also potentially support a more proactive approach of allowing melanocytes to recover in the skin. Sowe're really pleased with that. Safety from that study was very encouraging. Obviously, it's only 16 weeks of treatment for once-daily. We will continue that development program, but it's encouraging to this day.”

References

1. VYNE therapeutics announces dosing of first subject in phase 2b vitiligo trial of novel BET inhibitor VYN201. VYNE Therapeutics Inc. News release. June 5, 2024. Accessed June 5, 2024. https://vynetherapeutics.com/press-releases/vyne-therapeutics-announces-dosing-of-first-subject-in-phase-2b-vitiligo-trial-of-novel-bet-inhibitor-vyn201/
2. Andrus E, Stuart I. VYN201 for vitiligo: promising data showcases potential of BET inhibition. Dermatology Times. May 22, 2024. Accessed June 5, 2024. https://www.dermatologytimes.com/view/vyn201-for-vitiligo-promising-data-showcases-potential-of-bet-inhibition